DESCRIPTION Cell cycle regulation plays a critical role in controlling eukaryotic cell proliferation. Deregulating cell cycle events such as over- expression of cyclins and/or cyclin-dependent kinases (Cdks) or under- expression of Cdk inhibitors (CKIs) can lead to uncontrolled cell proliferation and malignancy. Inactivation of several Cdk inhibitors has been implicated in the development of some hereditary cancers including Retinoblastoma, Familial Adenomatous Polyposis, Von Hippel Lindau disease, and Wilm's tumor. In addition, Cdk inhibitors have been found to be mutated or deleted in a wide range of sporadic tumors. The long-term objectives of this proposal are to define the molecular cell cycle events and identify and characterize novel genes implicated in the development and progression of mouse gonadal tumorigenesis. This may lead to a better understanding of malignant progression in human ovarian and testicular cancers. The specific aims of this proposal are: 1) Define the cell cycle events involved in development and progression of ovarian and testicular cancer and inhibin-deficient mice: 2) Generate mice with multiple genetic lesions to study gonadal tumor development; 3) Identification and functional analysis of novel secreted and membrane gene products expressed in ovarian cancers.